title: Lack of laminin gamma1 in embryonic stem cell-derived cardiomyocytes causes inhomogeneous electrical spreading despite intact differentiation and function.
abstract: Laminins form a large family of extracellular matrix (ECM) proteins, and their expression is a prerequisite for normal embryonic development. Herein we investigated the role of the laminin gamma1 chain for cardiac muscle differentiation and function using cardiomyocytes derived from embryonic stem cells deficient in the LAMC1 gene. Laminin gamma1 (-/-) cardiomyocytes lacked basement membranes (BM), whereas their sarcomeric organization was unaffected. Accordingly, electrical activity and hormonal regulation were found to be intact. However, the inadequate BM formation led to an increase of ECM deposits between adjacent cardiomyocytes, and this resulted in defects of the electrical signal propagation. Furthermore, we also found an increase in the number of pacemaker areas. Thus, although laminin and intact BM are not essential for cardiomyocyte development and differentiation per se, they are required for the normal deposition of matrix molecules and critical for intact electrical signal propagation.
authors.affiliation: Institute of Physiology I, Life and Brain Center, University of Bonn, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Malan
authors.forename: Michael
authors.initials: M
authors.lastname: Reppel
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Dobrowolski
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Roell
authors.forename: Neil
authors.initials: N
authors.lastname: Smyth
authors.forename: Juergen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
mesh_terms: D000200:Action Potentials; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000378:metabolism; D004553:Electric Conductivity; D053595:Embryonic Stem Cells / Q000166:cytology*; D005109:Extracellular Matrix / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000172:deficiency*; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D016023:Integrins; D007797:Laminin; C089141:laminin gamma 1